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Objective This study aimed to (1) evaluate whether endothelial dysfunction, as measured by peripheral arterial tonometry (PAT) indices and biomarker (soluble fms-like tyrosine kinase-1 [sFLT], brain natriuretic peptide [BNP]) levels at 34 weeks gestation, can predict progression from nonsevere to severe hypertensive disorders of pregnancy (HDPs); and (2) develop a clinical risk model for prediction of progression from nonsevere to severe HDP.

Study Design We prospectively enrolled patients with a singleton gestation carrying a nonsevere HDP diagnosis. Forty-five participants were enrolled for PAT evaluation and serum collection between 340/7 and 366/7 weeks. PAT indices (e.g., Augmentation Index normalized to a heart rate of 75 bpm [AI75]) and biomarker concentrations were assessed at enrollment. The primary outcome was progression from a nonsevere diagnosis in the late preterm period to a diagnosis of preeclampsia with severe features or superimposed preeclampsia. Statistical analyses included two-sample t-tests, Fisher's exact tests, and multivariate modeling.

Results Thirteen subjects (30%) progressed to severe disease. No significant differences in mean PAT indices between the outcome groups were found. We found a significant difference in mean sFLT values between the two groups (p = 0.02, area under the curve [AUC] of 0.609), but not in mean BNP values. An endothelial dysfunction index (presence of fetal growth restriction, “high” AI75, and positive systolic blood pressure slope) discriminated between progression and nonprogression (p = 0.03, AUC of 0.707).

Conclusion sFLT level was a marker of progression from nonsevere to severe HDP. Further, a novel endothelial dysfunction index discriminated between progression and nonprogression to severe disease with good performance.

Key Points

HDPs are important causes of morbidity and mortality.

The sequelae of HDPs are not limited to pregnancy.

Developing accurate tools to predict severe HDPs is of great clinical importance.

Our index shows promising performance for predicting progression from nonsevere to severe HDPs.

Keywords peripheral arterial tonometry - fms-like tyrosine kinase-1 - brain natriuretic peptide - endothelial dysfunction - hypertensive disorders of pregnancy Data Availability

The data that support the findings of this study are available from the corresponding author, C.M.C., upon reasonable request.

Publication History

Received: 20 December 2023

Accepted: 29 August 2024

Article published online:
30 September 2024

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